Development of Fluorogenic Antioxidants to Monitor Reactive Oxygen Species in the Lipid Membrane of Live Cells

We have identified peroxyl radicals as key targets to monitor in our quest to reconcile the chemistry and biology of reactive oxygen species (ROS). In this context, we pioneered the development of lipophilic fluorogenic antioxidants for the spatiotemporal imaging of lipid peroxyl radicals in the membrane of live cells [1]. Our strategy involves preparing receptor-reporter probes that mimic the peroxyl radicalscavenging activity of α-tocopherol, the most active naturally occurring lipid soluble antioxidant present in mammalian tissues [2]. The receptor segment consists of the chromanol moiety of αtocopherol, ensuring the probe reactivity towards peroxyl radicals is on par with that of the antioxidant. A tethered borondipyrromethane dye (BODIPY) reports structural changes at the receptor end following peroxyl radical scavenging. BODIPY dyes are an ideal choice because they are lipophilic, photostable and easily prepared. Initially non-emissive, the probes become fluorescent once oxidation of chromanol to chromanone deactivates an otherwise operational intramolecular photoinduced electron transfer (PET) process [1].